Ultrasound capsule endoscopy: sounding out the future

Abstract

Video capsule endoscopy (VCE) has been of immense benefit in the diagnosis and management of gastrointestinal (GI) disorders since its introduction in 2001. However, it suffers from a number of well recognized deficiencies. Amongst these is the limited capability of white light imaging, which is restricted to analysis of the mucosal surface. Current capsule endoscopes are dependent on visual manifestation of disease and limited in regards to transmural imaging and detection of deeper pathology. Ultrasound capsule endoscopy (USCE) has the potential to overcome surface only imaging and provide transmural scans of the GI tract. The integration of high frequency microultrasound (µUS) into capsule endoscopy would allow high resolution transmural images and provide a means of both qualitative and quantitative assessment of the bowel wall. Quantitative ultrasound (QUS) can provide data in an objective and measurable manner, potentially reducing lengthy interpretation times by incorporation into an automated diagnostic process. The research described here is focused on the development of USCE and other complementary diagnostic and therapeutic modalities. Presently investigations have entered a preclinical phase with laboratory investigations running concurrently.

Keywords: Capsule endoscopy; diagnosis; gastrointestinal (GI); ultrasound (US); ultrasound capsule endoscopy (USCE).

Figure 1

A schematic of the ultrasound capsule endoscope (USCE) under development in the Sonopill programme. The 10 mm diameter ×30 mm long capsule, with spherical ends, will contain both ultrasound (component 2) and optical modalities (components 6 and 11). The ultrasound array is being developed as a high frequency or microultrasound transducer (>20 MHz) to facilitate transmural high resolution imaging of the bowel wall. Optical modalities include both white light imaging (component 11) and fluorescent imaging (component 2). Development of the fluorescent imaging cube is being conducted by Al-Rawhani and colleagues and is detailed in a separate publication (14). Additional development concerns other aspects of USCE, including electronic circuitry (components 3, 4 and 10) and power budget.

Figure 2

A schematic of ultrasound resolution and tissue penetration depicted from the lumen of the bowel outwards. There is a twofold effect as the ultrasound frequency is increased in terms of enhancing axial and lateral resolution with a proportional loss in depth of beam penetration (23) as indicated by scaled purple arrows. The diminished tissue penetration is a result of increased signal attenuation as a result of enhanced ultrasound wave to tissue interaction as frequency is increased. Conversely, the enhanced interaction results in improved axial and lateral resolution as finer structures become acoustically manifest and allows for improved discrimination between structures. The major advantages of using microultrasound in ultrasound capsule endoscopy (USCE) are the provision of high resolution images coupled with decreased penetration providing images pertaining directly to the gut wall.

Figure 3

A single element scan at 47.7 MHz and 40× magnification optical image of a hematoxylin and eosin (H&E) slide of porcine small bowel. The top image is across the short axis of an explanted small bowel section scanned in vitro. The mesenteric vessels have been cannulated and perfused with phosphate buffered saline (PBS) (32). The bottom image is a magnification of the microultrasound scan at 18–21 mm accompanied by an H&E image to demonstrate the fidelity in which micro-ultrasound can reconstruct tissue architecture. The scan depicts three distinct layers; namely the mucosa/submucosa, muscularis propria and serosa. The H&E slide depicts the four major layers with the mucosa and submucosa visibly separate. One reason for the lack of distinct upper layers in the scan may be the diminished interface difference between the mucosa and submucosa in the in vitro PBS perfused tissue.

Figure 4

A single element 47.7 MHz scan across the short axis of an explanted porcine small bowel section post infusion with phosphate buffered saline and hyperechogenic glass microspheres. The microspheres have accumulated subsurface (marked with red arrows) and have been detected qualitatively by the ultrasound transducer. Quantitative detection is indicated by the overlaid graph and indicates acoustic impedance (MRayl) changes specifically at the areas of microsphere aggregation. The infiltration of microspheres has resulted in a physical (i.e., acoustic) property change in the tissue allowing for quantitative detection of disruption. Additionally, there is a qualitative detection of the 90 µm polystyrene microsphere fiducial marker at 11 mm (red *) (Polysciences, USA) but there is a lack of quantitative signal. This is attributed to the depth of the marker lying below the region of interest segmentation of 100 µm. Of note is the qualitative imaging of the dilated capillaries (red +) lying below the aggregated microspheres which were used to infiltrate the glass microspheres.

Figure 5

A camera image and a 47.7 MHz scan of an explanted porcine esophagus and stomach. The scan is across the long axis of a full thickness porcine esophageal/gastric section at the gastroesophageal junction. The image and scan are not in scale with one another. The camera image illustrates the change from smooth stratified squamous lining of the distal third of the esophagus. The esophagus then keratinizes before transition into the stomach proper. The overlaid graph indicates attenuation changes across the scan as it passes from the esophagus to the stomach. There is a large change in the region of the gastroesophageal junction (red *) with an increase in attenuation at the area of cornification (red +). Scan results of the stomach are not shown.